Nov
Batten disease, a rare group of neurological disorders encompassing neuronal ceroid lipofuscinoses (NCLs), is a relentless condition that gradually worsens over time. It predominantly manifests in childhood, typically striking between the ages of 5 and 10, unless it’s the infantile or late infantile form, in which case symptoms usually surface before the child reaches the age of 1. This group of disorders is uniformly devastating, with a life expectancy tragically abbreviated, most often resulting in fatalities during the late teens or twenties. The speed at which this disease progresses and the associated risk of early death vary according to the specific form of Batten disease and the age of onset.
Batten disease wreaks havoc by instigating the accumulation of lipopigments, fatty substances, within the cells of the brain, central nervous system, and retinas. As a rare disease, it affects an estimated 2 to 4 out of every 100,000 infants born in the United States. Due to its genetic nature, it has the potential to afflict multiple members of the same family. Both parents must carry the gene to pass it on, and each of their children bears a one in four chance of inheriting the disease.
Understanding Batten Disease: A Spectrum of Challenges
Batten disease encompasses several forms, each characterized by its unique challenges. The symptoms common to these types encompass seizures, alterations in personality and behavior, progressive dementia, and the deterioration of speech and motor skills. While there is currently no cure for these disorders, there is a glimmer of hope on the horizon, as one of its forms, CLN2 disease, received FDA approval for an enzyme replacement therapy in 2017. This therapy, known as cerliponase alfa (Brineura), is a significant breakthrough.
Exploring the Four Major Types of Batten Disease
1. Congenital NCL: This exceptionally rare variant affects newborns, often leading to seizures and microcephaly, characterized by abnormally small heads. The prognosis is bleak, with most infants succumbing to the disease shortly after birth.
2. Infantile NCL (INCL, CLN1): INCL usually manifests between 6 months and 2 years of age, often with the onset occurring before the child’s first birthday. In addition to microcephaly, it can induce muscular contractions (jerks). Unfortunately, most children with INCL do not survive past early to mid-childhood. Juvenile-onset CLN1 may also emerge around age 5 or 6, progressing more slowly, potentially enabling affected individuals to live into their teenage years or even adulthood if symptoms arise during adolescence.
3. Late Infantile NCL (LINCL, CLN2): Typically commencing between the ages of 2 and 4, LINCL manifests with symptoms such as seizures and gradual loss of the ability to walk and speak. Regrettably, LINCL tends to be fatal between the ages of 8 to 12. In the case of CLN2 disease, treatment is available through cerliponase alfa (Brineura), a groundbreaking enzyme replacement therapy approved in 2017. Brineura serves to slow the decline in the ability to walk or crawl (ambulation) in symptomatic pediatric patients aged 3 and older who suffer from late infantile neuronal ceroid lipofuscinosis type 2 (CLN2). Brineura is administered into the cerebrospinal fluid via a specific surgically implanted reservoir and catheter in the head (intraventricular access device). Unfortunately, there are currently no treatments that can halt or reverse the progression of other NCL disorders.
4. CLN3 Disease: This form has a juvenile onset, typically emerging between the ages of 4 and 7. Patients experience progressive vision loss beginning between 4-7 years old, learning and behavioral issues, cognitive decline, and, around age 10, the onset of seizures. Antiseizure medications can help manage or reduce seizures. In their teenage years, affected individuals develop symptoms akin to Parkinsonism. Medications are available to address some of the parkinsonism symptoms, such as stiffness and difficulties with mobility and tasks. Unfortunately, most individuals with CLN3 disease pass away between the ages of 15 and 30.
5. Adult NCL (ANCL, CLN4 or Kufs Disease Type B): This variant typically initiates before the age of 40, in early adulthood. Patients with ANCL exhibit movement issues and early-stage dementia. While they tend to have shorter lifespans, the age at which they pass away can vary from person to person. Notably, ANCL does not lead to blindness.
Diagnosis and Testing for Batten Disease
Diagnosing Batten disease can be a challenging task, as it is a rare disorder, and numerous conditions share some of its symptoms. Typically, vision loss emerges as one of the earliest indicators, often leading eye doctors to be the first to suspect an issue. Several examinations and tests may be necessary before an accurate diagnosis is made. If a doctor suspects a need for further assessment, children are often referred to neurologists.
Various tests and assessments are employed in diagnosing Batten disease:
- Tissue Samples or Eye Examination: Examining tissue samples under a microscope enables doctors to identify the buildup of specific deposits, while certain deposits may also be observable in the eyes. Over time, these deposits can generate pink and orange circles, often referred to as a “bull’s eye.”
- Blood or Urine Tests: These examinations can detect particular abnormalities in blood and urine samples indicative of Batten disease.
- Electroencephalogram (EEG): An EEG involves affixing patches to the scalp to record the brain’s electrical currents and identify seizures.
- Imaging Tests: Computed tomography (CT) scans or magnetic resonance imaging (MRI) are instrumental in revealing brain changes that indicate Batten disease.
- DNA Test: If family history suggests the presence of Batten disease, a DNA test can confirm the diagnosis.
Treatment for Batten Disease: Overcoming Challenges
Currently, there is no known cure for any form of Batten disease. However, there is a glimmer of hope for those with CLN2 disease, thanks to the FDA’s approval of cerliponase alfa (Brineura) in 2017. While symptoms like seizures can be ameliorated with specific medications, other symptoms and associated issues can be managed through a combination of therapy and medications. Some individuals with Batten disease may benefit from physical or occupational therapy, enhancing their functional abilities.
The quest for more effective treatments and therapies is an ongoing endeavor, with scientists relentlessly researching potential options to alleviate the suffering of those affected by this cruel disease.
